TFAP2 paralogs regulate midfacial development in part through a conserved ALX genetic pathway.

Cranial neural crest development is governed by positional gene regulatory networks (GRNs). Fine-tuning of the GRN components underlies facial shape variation, yet how those networks in the midface are connected and activated remain poorly understood. Here, we show that concerted inactivation of Tfap2a and Tfap2b in the murine neural crest, even during the late migratory phase, results in a midfacial cleft and skeletal abnormalities. Bulk and single-cell RNA-seq profiling reveal that loss of both TFAP2 family members dysregulates numerous midface GRN components involved in midface morphogenesis, patterning and differentiation. Notably, Alx1, Alx3 and Alx4 (ALX) transcript levels are reduced, whereas ChIP-seq analyses suggest TFAP2 family members directly and positively regulate ALX gene expression. Tfap2a, Tfap2b and ALX co-expression in midfacial neural crest cells of both mouse and zebrafish implies conservation of this regulatory axis across vertebrates. Consistent with this notion, tfap2a zebrafish mutants present with abnormal alx3 expression patterns, Tfap2a binds ALX loci and tfap2a-alx3 genetic interactions are observed. Together, these data demonstrate TFAP2 paralogs regulate vertebrate midfacial development in part by activating expression of ALX transcription factor genes.

TFAP2 paralogs regulate midfacial development in part through a conserved ALX genetic pathway.

Cranial neural crest development is governed by positional gene regulatory networks (GRNs). Fine-tuning of the GRN components underly facial shape variation, yet how those in the midface are connected and activated remain poorly understood. Here, we show that concerted inactivation of Tfap2a and Tfap2b in the murine neural crest even during the late migratory phase results in a midfacial cleft and skeletal abnormalities. Bulk and single-cell RNA-seq profiling reveal that loss of both Tfap2 members dysregulated numerous midface GRN components involved in midface fusion, patterning, and differentiation. Notably, Alx1/3/4 (Alx) transcript levels are reduced, while ChIP-seq analyses suggest TFAP2 directly and positively regulates Alx gene expression. TFAP2 and ALX co-expression in midfacial neural crest cells of both mouse and zebrafish further implies conservation of this regulatory axis across vertebrates. Consistent with this notion, tfap2a mutant zebrafish present abnormal alx3 expression patterns, and the two genes display a genetic interaction in this species. Together, these data demonstrate a critical role for TFAP2 in regulating vertebrate midfacial development in part through ALX transcription factor gene expression.

Toward biodegradable nanogel star polymers via organocatalytic ROP.

Organocatalytic ring opening polymerization (OROP) is used to effect the rapid, scalable, room temperature formation of size-controlled, highly uniform, polyvalent, nanogel star polymer nanoparticles of biodegradable composition.