Vincentz et al., 2016, PNAS.pdf (1.72 MB)

Vincentz et al., 2016, PNAS.pdf

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journal contribution
posted on 06.03.2019 by Joshua Vincentz, Jianwen Que, Anthony B. Firulli

Cranial neural crest cells (crNCCs) migrate from the neural tube to the pharyngeal arches (PAs) of the developing embryo and, sub- sequently, differentiate into bone and connective tissue to form the mandible. Within the PAs, crNCCs respond to local signaling cues to partition into the proximo-distally oriented subdomains that convey positional information to these developing tissues. Here, we show that the distal-most of these subdomains, the distal cap, is marked by expression of the transcription factor Hand1 (H1) and gives rise to the ectomesenchymal derivatives of the lower incisors. We uncover a H1 enhancer sufficient to drive reporter gene expression within the crNCCs of the distal cap. We show that bone morphogenic pro- tein (BMP) signaling and the transcription factor HAND2 (H2) syner- gistically regulate H1 distal cap expression. Furthermore, the homeodomain proteins distal-less homeobox 5 (DLX5) and DLX6 reciprocally inhibit BMP/H2-mediated H1 enhancer regulation. These findings provide insights into how multiple signaling pathways di- rect transcriptional outcomes that pattern the developing jaw.

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