Why Does the Face Predict the Brain? Neural Crest Induction, Craniofacial Morphogenesis, and Neural Circuit Development

Abstract

Mesenchephalic and rhombencephalic neural crest cells generate the craniofacial skeleton, special sensory organs, and subsets of cranial sensory receptor neurons. They do so while preserving the anterior-posterior (A-P) identity of their neural tube origins. This organizational principle is paralleled by central nervous system circuits that receive and process information from facial structures whose A-P identity is in register with that in the brain. Prior to morphogenesis of the face and its circuits, however, neural crest cells act as “inductive ambassadors” from distinct regions of the neural tube to induce differentiation of target craniofacial domains and establish an initial interface between the brain and face. At every site of bilateral, non-axial secondary induction, neural crest constitutes all or some of the mesenchymal compartment for non-axial mesenchymal/epithelial (M/E) interactions. Thus, for epithelial domains in the craniofacial primordia, aortic arches, limbs, the spinal cord, and the forebrain (Fb), neural crest-derived mesenchymal cells establish local sources of inductive signaling molecules that drive morphogenesis and cellular differentiation. This common mechanism for building brains, faces, limbs, and hearts, A-P axis specified, neural crest-mediated M/E induction, coordinates differentiation of distal structures, peripheral neurons that provide their sensory or autonomic innervation in some cases, and central neural circuits that regulate their behavioral functions. The essential role of this neural crest-mediated mechanism identifies it as a prime target for pathogenesis in a broad range of neurodevelopmental disorders. Thus, the face and the brain “predict” one another, and this mutual developmental relationship provides a key target for disruption by developmental pathology.

Haplotype-Based Single-Step GWAS for Yearling Temperament in American Angus Cattle

“…The face morphogenesis biological process, annotated for the cysteine-rich secretory protein LCCL domain-containing 1 ( CRISPLD1 ) gene, was an interesting result. Neural crest cells are involved in face morphogenesis by generating the craniofacial skeleton, particularly the sensory organs and subsets of cranial sensory receptor neurons, and there are common mechanisms for building faces, brains, peripheral neurons, and central neural circuits that regulate behavioral functions [ 58 ]. In addition, the face structure has already been cited as a predictor of aggressiveness in humans, with the specific facial width-to-height ratio highly correlated with aggressiveness in men [ 59 ].…”

Lineage, Identity, and Fate of Distinct Progenitor Populations in the Embryonic Olfactory Epithelium

“…Our results suggest a novel role for an established inductive signaling mechanism that drives olfactory placode specification in parallel with that at other sites of non-axial mesenchymal/epithelial induction (reviewed by LaMantia, 2020). OE morphogenesis and ON differentiation reflects local signals from neural crest-derived mesenchyme or adjacent cranial ectoderm (Bhasin et al, 2003; Forni et al, 2013; LaMantia et al, 2000; Szabo-Rogers et al, 2009) as well as signals from the OE itself (Gokoffski et al, 2011) and amniotic fluid (AF) at the apical OE surface (Chau et al, 2015).…”

“…The apparent accumulation of Ascl1 Cre-E +/Ascl1-cells in the migratory mass suggests that OE precursors contribute to the frontonasal mesenchyme (fnm), a mosaic of cells with distinct molecular identities, and signaling capacity (reviewed by LaMantia, 2020). Medial, and some dorsolateral, fnm cells express Six1 ( Figure 4A ), while lateral fnm cells express Pax7 ( Figure 4B ).…”

“…Precursors may acquire additional identities or lineage capacity based upon time of origin, transcriptional history, position in the OE, or local signals. Regulation of monoallelic, regionally-restricted expression of odorant receptor genes (reviewed by Monahan and Lomvardas, 2015) might rely upon this sort of additional precursor diversity, perhaps established at the outset of OE differentiation when position and signaling in the olfactory placode and frontonasal mass, a fairly circumscribed embryonic domain, can impart significant instruction for subsequent development (Balmer and LaMantia, 2005; LaMantia, 2020). OE precursor diversity established at early stages might endure to support mosaic molecular distinctions in the mature OE.…”

Editorial: The Long Road to Building a Head: Smooth Travels and Accidents on the Journey From Patterning via Morphogenesis to Phenotype

“…It is the intricate temporal and spatial orchestration of these morphogenetic dynamics that brings about neural tube closure, creates additional layers from the pseudostratified cranial neuroectoderm to form different brain regions, facilitates neural crest delamination and migration, promotes accumulation of ectodermal cells to form sensory placodes, as well as enables the mesodermal and endodermal cell layer to shape muscles, connective tissues, blood vessels and endodermal lining. Accidents happening anywhere and anytime on that developmental road can impair head morphogenesis, leading to numerous types of craniofacial malformations and neurodevelopmental disorders ( LaMantia, 2020 ).…”