Atypical cadherins Celsr1-3 differentially regulate migration of facial branchiomotor neurons in mice

Yibo Qu1, Derrick M Glasco, Libing Zhou

  • 1Institute of Neuroscience, Developmental Neurobiology, Université Catholique de Louvain, Brussels, Belgium.

Insights

Cadherins Celsr1-3 and Fzd3 are crucial for facial branchiomotor neuron migration during hindbrain development. Celsr1 guides migration direction, while Celsr2 and Celsr3 control the ability to migrate.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Facial branchiomotor (FBM) neurons migrate during hindbrain development.
  • Planar cell polarity genes are implicated in FBM neuron migration in zebrafish.

Purpose of the Study:

  • Investigate the roles of cadherins Celsr1-3 and Fzd3 in mouse FBM neuron migration.
  • Determine the cell-autonomous or non-cell-autonomous functions of these genes.

Main Methods:

  • Analysis of Celsr1 (knock-out and Crash alleles) and Celsr2 mutant mice.
  • Conditional inactivation of Celsr genes in FBM neurons.
  • Assessment of FBM neuron migration patterns and hindbrain patterning.

Main Results:

  • Celsr1 mutations disrupted caudal migration, causing rostral and lateral misplacement of FBM neurons.
  • Celsr1 function in FBM neuron migration is non-cell autonomous.
  • Celsr2 mutations led to premature lateral migration, an effect enhanced by Celsr3 inactivation.
  • Fzd3 inactivation mimicked Celsr2 phenotypes, and Celsr2 was epistatic to Celsr1.

Conclusions:

  • Celsr1, Celsr2, and Celsr3 play distinct roles in FBM neuron migration.
  • Celsr1 specifies migration direction, while Celsr2 and Celsr3 regulate migration execution.

Related Concept Videos

Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
Cell Migration01:09

Cell Migration

Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
Cytoskeletal Coordination in Cell Migration01:32

Cytoskeletal Coordination in Cell Migration

A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker proteins that...
Structure of Cadherins01:25

Structure of Cadherins

The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins”   is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...
Determination01:51

Determination

During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In contrast, determination...