Molecular Control of Neurogenesis 

Research

We are currently exploring the origin of adult NSCs in the dentate gyrus during postnatal development using innovative strategies such as spatial RNA-Seq analysis, a mouse line reporting quiescence, and the involvement of astrocytes in the generation of adult NSCs. In addition, we are performing behavioural assays in mice to determine the involvement of Sox5 loss in spatial and social memory.

Proneurogenic strategies

Our group has collaborated in the discovery of new pro-neurogenic drugs using adult NSCs in culture (Salado et al., 2017; Uliassi et al., 2019). Among them, a group of LRRK2 inhibitors that control the proliferation of adult NSCs and promote oligodendroglial fate (Zaldívar-Diez et al., 2020), which is of great interest in therapies for demyelinating diseases. All these studies are highly relevant for promoting neurogenesis in the adult human brain, especially in neurodevelopmental and neurodegenerative diseases or during ageing.

We are currently collaborating with Sophie Morse of Imperial College to explore the neurogenic potential of selective disruption of the blood-brain barrier in the hippocampus.

Neurodevelopmental disorders

Another important objective of our laboratory is to understand the pathophysiological basis of neurodevelopmental disorders, such as Lamb-Shaffer syndrome (LAMSHF), a rare disease caused by mutations in the SOX5 gene. LAMSHF is characterised by alterations in the central nervous system, such as cognitive deficits, significant speech delay, visual system defects, anxiety and autism spectrum behaviours (ASD), which include repetitive behaviours and deficits in social interaction. Our laboratory has generated several mouse models with conditional loss of Sox5 in the central nervous system. We have established that the loss of Sox5 in the hippocampal CA2 region alters social memory (Rodríguez-Martín et al., in preparation; Fundación Koplowitz project).

In collaboration with the Spanish LAMSHF Association and Dr Lapunzina’s group (La Paz Hospital), we have identified the first 20 Spanish patients with LAMSHF (Tenorio-Castano et al., 2023). We are currently collaborating with them to support families and promote research through projects such as those of the Inocente Inocente Foundation (2024) and the FEDER Foundation (2025). We have also recently begun analyses to understand the basis of another neurodevelopmental disorder, Tolchin-Le Caigne Syndrome (caused by mutations in the SOX6 gene) and characterised by patients presenting with epileptic seizures, hyperactivity and  early Parkinson’s disease, amongst others.

Team

I grew up in Córdoba (Spain), where I graduated as a Veterinary. However, as I had always been interested in research, I came to Madrid to do my PhD at Flora de Pablo and Enrique de la Rosa laboratory at the CIB (CSIC). By that time, we discovered that insulin is a survival factor during embryonic development. After completing my thesis, I obtained a Marie Curie contract for my first postdoc in David Ish-Horowicz’s laboratory at the ICRF (Cancer Research UK) in London, working on the molecular clock controlling somitogenesis. Upon my return to Spain, I joined Angela Nieto’s laboratory at the Cajal Institute (CSIC), demonstrating that genes from the Snail family participate in the formation of somites and in the survival of neural crest cells.

Since 2005, first with a Ramón y Cajal contract and then as a Scientific Researcher, I have run my own laboratory focusing on different aspects of nervous system development. We have been working on the specification and migration of neural crest cells, the establishment of the dorsoventral pattern in the spinal cord and, more recently, on the molecular control of adult hippocampal neurogenesis. Moreover, in collaboration with the Lamb-Shaffer Syndrome Patient Foundation, we are exploring hippocampal alterations in this neurodevelopmental disorder using mouse models and human iPSCs. In my spare time, I enjoy travelling with my family, learning watercolour painting and outdoor running.

Paula holds a Degree in Biology from Universidad Autónoma de Madrid and a Master in Neuroscience from the same university. She joined our laboratory in 2022 with a predoctoral fellowship in Neuroscience from the Tatiana Pérez de Guzmán el Bueno Foundation to study the establishment of the hippocampal neural stem cell niche during postnatal development.

Pilar studied Biotechnology at the University of Salamanca and later got a MSc in Health Biotechnology with Cellular Therapy specialization at Pablo de Olavide University in Seville. She joined the lab in 2021 with a “Garantia Juvenil” contract from the Community of Madrid and now she is pursuing a PhD in Molecular Biology. She studies hippocampal alterations in loss-of-Sox5 mouse models of Lamb-Shaffer syndrome, conducting both behavioral and molecular approaches. When she´s not in the lab, she enjoys birdwatching, playing video games, and spending time on her sewing machine.

Sofía holds a Degree in Biology from Universidad Autónoma de Madrid. She obtained a Master’s degree in Biochemistry, Molecular Biology, and Biomedicine from Universidad Complutense de Madrid. She joined the laboratory in 2025 to develop her doctoral thesis thanks to a predoctoral grant from Plan Estatal de Investigación, associated with the Molecular Biosciences doctoral program. Her studies focus on exploring the function of Sox5 in astrocytes and its possible role in the transition from developmental to adult neural stem cells in the dentate gyrus.

Laura is a Senior Technician in Clinical Diagnostic Laboratory. In 2010, she began working in a cardiovascular research group at the Universidad Autónoma de Madrid. In 2015, she joined the Centro Nacional de Investigaciones Oncológicas (CNIO), where she specialized in the search for new treatments for lung cancer. She joined our laboratory in 2024, where she contributes her experience in in vivo and in vitro approaches to different lines of research. When she leaves the lab, Laura enjoys writing, cooking and listening to music.

Laura graduated in Biochemistry from the Complutense University of Madrid and is continuing her studies with a Master’s degree in Neuroscience at the Autonomous University of Madrid. She joined the laboratory in 2024 with a JAE-Intro scholarship and is currently working on her Master’s Thesis, which focuses on studying the role of Sox5 and the TGFβ pathway in establishing stem cell quiescence during development. Outside the laboratory, she enjoys spending time drawing, rock climbing, and playing electric guitar.

Exmembers

Recent publications

• Sox5 controls the establishment of quiescence in neural stem cells during postnatal development. (2025). Medina-Menéndez, C., Tirado-Melendro, P.,  Li, L., Rodríguez-Martín, P., Melgarejo, E., Díaz, M., Valdés-Bescós, M., López-Sansegundo, R. and Morales,A.V. Plos Biology 3002654. Publication

• Lamb-Shaffer syndrome: 20 Spanish patients and literature review expands the view of neurodevelopmental disorders caused by SOX5 haploinsufficienc. (2023) Tenorio-Castano, J., Sánchez-Algaba Gómez, A., Coronado, M., Rodríguez-Martín, P., Parra, A., Pascual, P., Cazalla, M., Gallego, N., Arias, P., Morales, A.V.,  Nevado, J., Lapunzina, P.  Clinical Genetics 104:637-647. Publication

• SoxD genes are required for adult neural stem cell activation. (2022) Li, L.*, Medina-Menéndez, C.*, García-Corzo, L., Quiroga, A.C., Calleja, E., Córdoba, C., Zinchuk, V., Muñoz, S., Rodríguez-Martín, P., Ciorraga, M., Colmena, I., Fernández, S., Vicario-Abejón, C., Nicolis S., Lefebvre, V., Mira, H. and Morales, AV. Cell Reports 38:110313. [Portada]. (* equal contribution). Publication  

• Sublayer- and cell-type-specific neurodegenerative transcriptional trajectories in hippocampal sclerosis. (2021). E. Cid, A. Márquez-Galera, M. Valero, B. Gal, D. C. Medeiros, C. M. Navarrón, L. Ballesteros-Esteban, R. Reig-Viader, Morales, A.V. L. Dolon, I. Fernandez-Lamo, D. Gomez-Dominguez, M. Sato, Y. Hayashi, À. Bayés, A. Barco, J. P López-Atalaya, L. M de la Prida. Cell Reports 35(10):109229 Publication
  

• Editorial: Generation of Neurons and Their Integration in Pre-existing Circuits in the Postnatal Brain: Signalling in Physiological and Regenerative Contexts. (2020). Mira H, Diez Del Corral R, Morales, A.V. Front Cell Dev Biol. 8:560 (2020) Electronic Book Collection 2020. Publication

• Benzothiazole-based LRRK2 inhibitors as WNT enhancers and promoters of oligodendrocytic fate. (2020). Zaldivar-Diez, J., Li, L., García, A.M., Zhao , W., Medina-Menendez, C., Haggarty, S.J., Gil, C., Morales, A.V.* and Martinez, A*. (*corresponding authors). Journal of Medicinal Chemistry 63(5):2638-2655. Publication

• Adult neural stem cells: born to last. (2019). A. V. Morales, and H. Mira. Front. Cell Dev. Biol. Jun 4;7: 96 Publication
  

• Proximodistal organization of the CA2 hippocampal area. (2019). I. Fernandez-Lamo, D. Gomez-Dominguez, A. Sanchez-Aguilera, A. Oliva, A. V. Morales, M. Valero, E. Cid, A. Berenyi and L. Menendez de la Prida.Cell Reports 26 (7): 1734-1746 [Cover] Publication
  

• A focused library of psychotropic analogs with neuroprotective and neuroregenerative potential. (2019). Uliassi, E.; Peña-Altamira, L. E.; Morales, A.V.; Massenzio, F.; Petralla, S; Rossi, M; Roberti, M.; Martinez Gonzalez, L.; Martínez, A.; Monti, B.; Bolognesi, M. L. ACS Chemical Neuroscience Jan 16;10(1):279-294. Publication 

• GLI1 Inactivation is associated with Developmental Phenotypes Overlapping with Ellis-Van Creveld Syndrome (2017).A. Palencia-Campos, A. Ullah, J.Nevado, R. Yıldırım, E.Unal, M. Ciorraga, P., Lucia Chico, F. Piceci-Sparascio, V. Guida, A. De Luca, H. Kayserili, I. Ullah, M. Burmeister, P. Lapunzina, W. Ahmad, Morales, A.V., V. L. Ruiz-Perez. Human Molecular Genetics. 26(23):4556-4571. [Cover] Publication

• Leucine Rich Repeat Kinase 2 (LRRK2) Inhibitors based on indolinone scaffold: Potential Pro-neurogenic Agents. (2017). Salado, I.G., Zaldivar-Diez, J., Sebastian, V., Li, L., Geiger, L., González, S., Campillo, N.E., Morales, A.V.,, Perez, D.I. and Martinez, A. European Journal of Medicinal Chemistry 138:328-342. Publication

• The multiple roles of FGF signaling in the extending spinal cord. (2017). Diez del Corral, R. and Morales, A.V. Front. Cell Dev. Biol. Jun 2;5:58. Publication
  

• Brain insulin-like growth factor-I directs the transition from stem cells to mature neurons during postnatal/adult hippocampal neurogenesis. (2016). Nieto-Estevez, V, Oueslati-Morales, C.O., Li, L., Pickel, J., Morales, A.V., and Vicario-Abejon. Stem Cells 34(8):2194-209. Publication
  

• FGF signaling enhances a Shh negative feedback loop to coordinate ventral patterning and caudal extension of the spinal cord.(2016). Morales, A.V., Espeso-Gil, S., Ocaña, I., Nieto-López, F., Calleja, E., Bovolenta, P., Lewandoski, M. and Diez del Corral, R. Developmental Neurobiology 76(9):956-71. Publication 

• Neural development and regeneration: it’s all in your spinal cord. (2015). Becker CG, Diez Del Corral R. Development 142: 811-816. Publication
  

• Sox5 controls dorsal progenitor and interneuron specification in the spinal cord. (2014).Quiroga AC, Stolt CC, Diez del Corral R, Dimitrov S, Perez-Alcala S, Sock E, Barbas JA, Wegner M, Morales AV. Developmental Neurobiology. 75(5):522-38 (2015)Publication

• Retinoic Acid Signaling during Early Spinal Cord Development. (2014).Morales AV, Diez del Corral R. Journal  Developmental Biology 2: 174-197. Publication
  

• FGF and retinoic acid activity gradients control the timing of neural crest cell emigration in the trunk. (2011). Martinez-Morales, P.L., Diez Del Corral, R., Olivera-Martinez, I., Quiroga, A.C., Das, R.M., Barbas, J.A., Storey, K.G., and Morales, A.V. Jounal Cell Biology. 194:489-503. Publication
  

• Coordination of Cell Differentiation and Migration in Mathematical Models of Caudal Embryonic Axis Extension. (2011). Harrison, N.C., Diez del Corral, R.*, and Vasiev, B.*PLoS ONE 6, e22700.*Co-corresponding authors. Publication
  

• SOX5 controls cell cycle progression in neural progenitors by interfering with the WNT-beta-catenin pathway.(2010). Martinez-Morales, P.L., Quiroga, A.C., Barbas, J.A., and Morales, A.V. EMBO Reports 11, 466-472. Publication
  

• Snail genes at the crossroads of symmetric and asymmetric processes in the developing mesoderm (2007). Morales AV, Acloque H, Ocaña OH, de Frutos CA, Gold V and Nieto MA. EMBO Reports. 8:104-109 [Portada]. Publication
  

• How to become neural crest: from segregation to delamination (2005) Morales AV, Barbas JA, Nieto MA. Semin Cell Dev Biol. 16(6):655-62. Publication
  

• LSox5 regulates RhoB expression in the neural tube and promotes generation of the neural crest (2004). Perez-Alcala S, Nieto MA, Barbas JA. Development 131(18):4455-65. Publication
  

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