research

We study the cellular and molecular mechanisms regulating cell fate decisions at the neural plate border. In the vertebrate embryo, the neural plate border defines a competence domain established between neural (prospective central nervous system) and non-neural (future epidermis) ectoderm. Within this domain signaling events progressively direct the emergence of two cell populations, the neural crest and cranial placodes. In the head region neural crest derivatives include cartilages and bones of the face, the middle ear ossicle and some cranial ganglia. The cranial placodes contribute to the paired sensory organs (olfactory epithelium, inner ear and lens), the adenohypophysis, and a subset of cranial ganglia including the trigeminal ganglion, which provides sensory innervation to the orofacial complex.

Using Xenopus as a model system, our goal is to identify the gene regularory network driving neural crest and placode fates. Because neural crest and placode progenitors make a major contribution to head structures and sensory organs, defining how these processes are regulated is essential to gain insights into the etiology and pathogenesis of congenital disorders affecting craniofacial development.

 

Xenopus as a model system to study gene function

The frog Xenopus laevis is an extremely powerful system to investigate the molecular mechanisms underlying gene function. The large size of the Xenopus embryo and its development outside of the body of the female makes it an ideal system to alter gene function by microinjection of mRNA or morpholino antisense oligonucleotides. The first cleavage divides the Xenopus embryo along the left/right axis, therefore injection of one cell at the 2-cell stage can affect gene function in only one side of the embryo, while the other side serves as an internal control. The Xenopus animal cap assay using blastula stage explants that can be excised and cultured in vitro has especially proven to be a remarkably versatile system to assess the ability of exogenously expressed transcription factors or signaling molecules to influence patterns of gene expression using a variety of molecular techniques. Finally, TALEN and CRISPR/Cas9 technologies have been successfully used to introduce targeted modifications in Xenopus genome.

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