MCDB










The Origin of Neural Crest Cells
Martin Garcia-Castro, Ph.D.

Martín García–Castro, Ph.D.

Associate Professor of Molecular, Cellular, & Developmental Biology
KBT 1100
Email: martin.garcia-castro@yale.edu
Phone: (203) 432-3523

B.S. ENEP Iztacala UNAM; M.S. IBB UNAM MEXICO; Ph.D. Cambridge University, UK; Postdoctoral Fellow
California Institute of Technology. USA.

 

 

Double in site hybridization for Pax 7 (dark blue) and Wnt8c (cyan) and Tbx6L (dark red.)

Cryosection showing migratory neural crest and condensing ganglia (HNK1, green) and injected DiI-abeled cells.

Central to the development of vertebrates is the neural crest, a dynamic stem cell–like population that arises at the border of the neural plate early in development, migrates considerable lengths through defined paths, and differentiates into a plethora of cell–types. Neural crest derivatives include neurons and glial–cells of the peripheral nervous system, melanocytes, endocrine cells, and cranio-facial bone and cartilage. Neural crest cells are responsible for several health complications, ranging from brain tumors and cancer to craniofacial and cardiac outflow–tract malformations. Therefore, neural crest cells are an excellent subject of study for fundamental topics of developmental biology, such as induction, specification, potency, fate, regulation, and migration.

Our laboratory is interested in understanding the development of neural crest cells at the tissue, cell, and molecular level, and our first goal is to understand when, where, and how neural crest cells originate. Contemporary models suggest that prospective neural tissue can be modified by surrounding tissues (lateral epidermal-ectoderm or underlying mesoderm) to generate neural crest. At the molecular level, Wnt and BMP signals have been identified as critical players during neural crest induction. Most of our knowledge regarding induction in aminiotes concerns trunk neural crest formation. The limited information regarding the origin and induction of cranial neural crest cells is astonishing, given that only cranial crest cells have the potential to generate bone and cartilage of the head. The nature of this difference is unknown, as well as the time and conditions that surround the induction of cranial neural crest. It is therefore critical to investigate the conditions surrounding the origin of neural crest cells at different axial levels.

We are currently addressing the following topics:

  1. Earliest events of cranial and trunk neural crest induction.
  2. Interactions between BMP and Wnt signaling molecules during neural crest induction.
  3. Comparative analysis of cranial and trunk neural crest induction.

We are investigating the precise participation of cells, tissues, and molecules in neural crest development using cell and molecular biology, imaging technologies (confocal, time-lapse), and modern and traditional embryology. For example, we inject embryos with dyes, viruses, and cells, we electroporate oligonucleotides and plasmids, we graft beads and tissues, and we perform in vitro culture of tissue explants.

Selected Publications

Stuhlmiller, T., García–Castro, M.I. (2012) "FGF/MAPK signaling is required in the gastrula epiblast for avian neural crest induction" Development 139, 289–300, recently Selected and recommended by Faculty of a Thousand.

Betters, E., Liu, Y., Kjaeldgaard, A., Sundström, E., and García–Castro, M. I. (2010) "Analysis of early human neural crest development" Developmental Biology 344 (2): 578–592

Murdoch, B., DelConte, C., and García–Castro, M. I. (2010) "Embryonic Pax7–expressing progenitors contribute multiple cell types to the postnatal olfactory epithelium" J. Neuroscience 30: 9523-9532

Basch, M., Bronner-Fraser, M. and García–Castro, M.I. (2006) "Specification of the neural crest occurs during gastrulation and requires Pax7" Nature 441:218-222. Featured by D. McGowan in Research Highlights for the journal Nature Reviews/ Neuroscience 7:1 and Selected by three reviewers for Faculty of a 1000 as a must read.

García–Castro, M.I., Marcelle, C., and Bronner–Fraser, M. (2002) "Wnt in the ectoderm functions as a neural crest inducer" Science 297, 848-851. Featured by Trainor and Krumlauf in Development Perspectives, Science 297:781, and selected by three reviewers for Faculty of a Thousand as a must read.

García–Castro, M.I., Vielmetter, E. and Bronner–Fraser, M. (2000). "N–Cadherin, a Cell Adhesion Molecule Involved in Establishment of Embryonic Left–Right Asymmetry". Science 288, 1047–1051.

Slug expression (dark blue) is inhibited by DNwnt1-expressing cells (brown.)

Activtion of electroporated Wnt reporter RFP

 

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