Chapter Seven - Celsr1–3 Cadherins in PCP and Brain Development

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Abstract

Cadherin EGF LAG seven-pass G-type receptors 1, 2, and 3 (Celsr1–3) form a family of three atypical cadherins with multiple functions in epithelia and in the nervous system. During the past decade, evidence has accumulated for important and distinct roles of Celsr1–3 in planar cell polarity (PCP) and brain development and maintenance. Although the role of Celsr in PCP is conserved from flies to mammals, other functions may be more distantly related, with Celsr working only with one or a subset of the classical PCP partners. Here, we review the literature on Celsr in PCP and neural development, point to several remaining questions, and consider future challenges and possible research trends.

Section snippets

Celsr1–3 Expression Patterns

In mammals, the Celsr family is composed of three members, whereas birds apparently lack Celsr2 (Formstone, 2010) and fish have two, Celsr1a and 1b (Wada, Tanaka, Nakayama, Iwasaki, & Okamoto, 2006). In the mouse, Celsr13 genes have similar genomic organizations, with 35 (Celsr1 & Celsr3) or 34 exons (Celsr2). Apart from 3′ alternative exons in Celsr2, alternative splicing has not been described. Celsr13 expression is regulated spatially and temporally, indicating that they are important for

Celsr1: A Major Player in Vertebrate PCP

Two Celsr1 mutant alleles, Crash (Celsr1Crsh) and Spin Cycle (Celsr1Scy), were identified in an ENU screen (Curtin et al., 2003). In Celsr1Crsh, a G-to-A mutation at nucleotide 3126 results in an aspartate-to-glycine substitution in codon 1040, within the eighth cadherin repeat. In Celsr1Scy, a T-to-A point mutation at nucleotide 3337 results in an asparagine-to-lysine substitution in codon 1110, in a region connecting cadherin repeats. Heterozygous animals show abnormal head-shaking behavior.

Celsr2 and 3 in Ciliogenesis

Cilia are appendages that extend from the cell surface to the extracellular environment. Based on their structure and motility, cilia are classified into three types: motile, primary, and nodal cilia (Davenport & Yoder, 2005). Motile cilia garnish the apical surface of epithelial cell lining airways, reproductive tracts, and cerebral ventricles. They have a central pair of microtubules surrounded by nine doublet of microtubules, an organization known as 9 + 2, and are anchored to a basal body in

Celsr1–3 in Neuronal Migration

The migration of facial branchiomotor (FBM) neurons in the developing rhombencephalon is an intriguing case that combines tangential and radial migration modes. FBM neurons, which innervate muscles responsible for facial expression (Chandrasekhar, 2004, Garel et al., 2000, Guthrie, 2007), are generated in medial rhombomere4 (r4) at E10.5 and immediately extend their axons laterally toward muscle targets. At E11.5, their cell bodies initiate a tangential caudal migration from r4 to r6. They

Celsr2 and Celsr3 in Brain Wiring

Functional neuronal networks are crucial for brain function. Network formation is finely orchestrated at the cellular and molecular levels by genetic programs and interactions with the environment. After reaching their location, postmitotic neurons extend axons that are guided to their targets by intrinsic programs, guidepost cells, and attractive and repulsive molecular cues. They ramify receptive dendritic fields according to tiling rules. In addition to their role in neuronal migration,

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