ZFIN ID: ZDB-PUB-200524-3
Cell-fate plasticity, adhesion and cell sorting complementarily establish a sharp midbrain-hindbrain boundary
Kesavan, G., Machate, A., Hans, S., Brand, M.
Date: 2020
Source: Development (Cambridge, England)   147(11): (Journal)
Registered Authors: Brand, Michael, Hans, Stefan, Kesavan, Gokul, Machate, Anja
Keywords: Cell adhesion and Ephrin signaling, Cell sorting, Midbrain-hindbrain boundary (MHB), Zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified/growth & development
  • Animals, Genetically Modified/metabolism
  • CRISPR-Cas Systems/genetics
  • Cadherins/genetics
  • Cadherins/metabolism
  • Cell Adhesion/physiology*
  • Cell Lineage
  • Embryo, Nonmammalian/metabolism
  • Ephrins/antagonists & inhibitors
  • Ephrins/genetics
  • Ephrins/metabolism
  • Gastrulation
  • Gene Editing
  • Mesencephalon/metabolism*
  • Mesencephalon/pathology
  • Microscopy, Atomic Force
  • Microscopy, Fluorescence
  • Morpholinos/metabolism
  • Otx Transcription Factors/genetics
  • Otx Transcription Factors/metabolism
  • Rhombencephalon/metabolism*
  • Rhombencephalon/pathology
  • Signal Transduction
  • Time-Lapse Imaging
  • Zebrafish/growth & development
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 32439756 Full text @ Development
The formation and maintenance of sharp boundaries between groups of cells play a vital role during embryonic development as they serve to compartmentalize cells with similar fates. Some of these boundaries also act as organizers, with the ability to induce specific cell fates and morphogenesis in the surrounding cells. The midbrain-hindbrain boundary (MHB) is such an organizer that also acts as a lineage restriction boundary to prevent the intermingling of cells with different developmental fates. However, the mechanisms underlying the lineage restriction process remain unclear. Here, using novel fluorescent knock-in reporters, live imaging, Cre/lox-mediated lineage tracing, atomic force microscopy-based cell adhesion assays, and mutant analysis, we analyze the process of lineage restriction at the MHB and provide mechanistic details. Specifically, we show that lineage restriction occurs by the end of gastrulation, and that the subsequent formation of sharp gene expression boundaries in the developing MHB occur through complementary mechanisms, namely cell-fate plasticity and cell sorting. Further, we show that cell sorting at the MHB involves differential adhesion among midbrain and hindbrain cells that is mediated by N-cadherin and Eph-Ephrin signaling.