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Graded levels of Pax2a and Pax8 regulate cell differentiation during sensory placode formation.

ABSTRACT: Pax gene haploinsufficiency causes a variety of congenital defects. Renal-coloboma syndrome, resulting from mutations in Pax2, is characterized by kidney hypoplasia, optic nerve malformation, and hearing loss. Although this underscores the importance of Pax gene dosage in normal development, how differential levels of these transcriptional regulators affect cell differentiation and tissue morphogenesis is still poorly understood. We show that differential levels of zebrafish Pax2a and Pax8 modulate commitment and behavior in cells that eventually contribute to the otic vesicle and epibranchial placodes. Initially, a subset of epibranchial placode precursors lie lateral to otic precursors within a single Pax2a/8-positive domain; these cells subsequently move to segregate into distinct placodes. Using lineage-tracing and ablation analyses, we show that cells in the Pax2a/8+ domain become biased towards certain fates at the beginning of somitogenesis. Experiments involving either Pax2a overexpression or partial, combinatorial Pax2a and Pax8 loss of function reveal that high levels of Pax favor otic differentiation whereas low levels increase cell numbers in epibranchial ganglia. In addition, the Fgf and Wnt signaling pathways control Pax2a expression: Fgf is necessary to induce Pax2a, whereas Wnt instructs the high levels of Pax2a that favor otic differentiation. Our studies reveal the importance of Pax levels during sensory placode formation and provide a mechanism by which these levels are controlled.

SUBMITTER: McCarroll MN

PROVIDER: S-EPMC3392703 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Graded levels of Pax2a and Pax8 regulate cell differentiation during sensory placode formation.

McCarroll Matthew N MN Lewis Zachary R ZR Culbertson Maya Deza MD Martin Benjamin L BL Kimelman David D Nechiporuk Alex V AV

Development (Cambridge, England) 20120628 15

Pax gene haploinsufficiency causes a variety of congenital defects. Renal-coloboma syndrome, resulting from mutations in Pax2, is characterized by kidney hypoplasia, optic nerve malformation, and hearing loss. Although this underscores the importance of Pax gene dosage in normal development, how differential levels of these transcriptional regulators affect cell differentiation and tissue morphogenesis is still poorly understood. We show that differential levels of zebrafish Pax2a and Pax8 modul ...[more]

PMID: 22745314

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Project description:The vertebrate peripheral nervous system contains sensory neurons that arise from ectodermal placodes. Placodal cells ingress to move inside the head to form sensory neurons of the cranial ganglia. To date, however, the process of placodal cell ingression and underlying cellular behavior are poorly understood as studies have relied upon static analyses on fixed tissues. Visualizing placodal cell behavior requires an ability to distinguish the surface ectoderm from the underlying mesenchyme. This necessitates high resolution imaging along the z-plane which is difficult to accomplish in whole embryos. To address this issue, we have developed an imaging system using cranial slices that allows direct visualization of placode formation.We demonstrate an effective imaging assay for capturing placode development at single cell resolution using chick embryonic tissue ex vivo. This provides the first time-lapse imaging of mitoses in the trigeminal placodal ectoderm, ingression, and intercellular contacts of placodal cells. Cell divisions with varied orientations were found in the placodal ectoderm all along the apical-basal axis. Placodal cells initially have short cytoplasmic processes during ingression as young neurons and mature over time to elaborate long axonal processes in the mesenchyme. Interestingly, the time-lapse imaging data reveal that these delaminating placodal neurons begin ingression early on from within the ectoderm, where they start to move and continue on to exit as individual or strings of neurons through common openings on the basal side of the epithelium. Furthermore, dynamic intercellular contacts are abundant among the delaminating placodal neurons, between these and the already delaminated cells, as well as among cells in the forming ganglion.This new imaging assay provides a powerful method to analyze directly development of placode-derived sensory neurons and subsequent ganglia formation for the first time in amniotes. Viewing placode development in a head cross-section provides a vantage point from which it is possible to study comprehensive events in placode formation, from differentiation, cell ingression to ganglion assembly. Understanding how placodal neurons form may reveal a new mechanism of neurogenesis distinct from that in the central nervous system and provide new insight into how cells acquire motility from a stationary epithelial cell type.

Dataset Information

Graded levels of Pax2a and Pax8 regulate cell differentiation during sensory placode formation.

Publications

Graded levels of Pax2a and Pax8 regulate cell differentiation during sensory placode formation.

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