Tissue-specific activities of the Fat1 cadherin cooperate to control neuromuscular morphogenesis

PLoS Biology
Françoise Helmbacher

Abstract

Muscle morphogenesis is tightly coupled with that of motor neurons (MNs). Both MNs and muscle progenitors simultaneously explore the surrounding tissues while exchanging reciprocal signals to tune their behaviors. We previously identified the Fat1 cadherin as a regulator of muscle morphogenesis and showed that it is required in the myogenic lineage to control the polarity of progenitor migration. To expand our knowledge on how Fat1 exerts its tissue-morphogenesis regulator activity, we dissected its functions by tissue-specific genetic ablation. An emblematic example of muscle under such morphogenetic control is the cutaneous maximus (CM) muscle, a flat subcutaneous muscle in which progenitor migration is physically separated from the process of myogenic differentiation but tightly associated with elongating axons of its partner MNs. Here, we show that constitutive Fat1 disruption interferes with expansion and differentiation of the CM muscle, with its motor innervation and with specification of its associated MN pool. Fat1 is expressed in muscle progenitors, in associated mesenchymal cells, and in MN subsets, including the CM-innervating pool. We identify mesenchyme-derived connective tissue (CT) as a cell type in which Fat1 a...Continue Reading

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Citations

Dec 11, 2019·Tissue Barriers·Sophia K TheodossiouNathan R Schiele
Jun 11, 2020·Seminars in Cell & Developmental Biology·Françoise Helmbacher, Sigmar Stricker

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Methods Mentioned

BETA
genetrap
transgenic
dissection
biopsies
fluorescence imaging

Software Mentioned

Zen
NMJ
Axiovision
ImageJ
Image J
StatEL
Excel
Zen Imaging

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