Journal Article

Celsr3 drives development and connectivity of the acoustic startle hindbrain circuit

Ortiz, Elelbin A., Meserve, Joy H., Navarro, Maria F., Granato, Michael

2024

Overview

In the developing brain, groups of neurons organize into functional circuits that direct diverse behaviors. One such behavior is the evolutionarily conserved acoustic startle response, which in zebrafish is mediated by a well-defined hindbrain circuit. While numerous molecular pathways that guide neurons to their synaptic partners have been identified, it is unclear if and to what extent distinct neuron populations in the startle circuit utilize shared molecular pathways to ensure coordinated development. Here, we show that the planar cell polarity (PCP)-associated atypical cadherins Celsr3 and Celsr2, as well as the Celsr binding partner Frizzled 3a/Fzd3a, are critical for axon guidance of two neuron types that form synapses with each other: the command-like neuron Mauthner cells that drive the acoustic startle escape response, and spiral fiber neurons which provide excitatory input to Mauthner cells. We find that Mauthner axon growth towards synaptic targets is vital for Mauthner survival. We also demonstrate that symmetric spiral fiber input to Mauthner cells is critical for escape direction, which is necessary to respond to directional threats. Moreover, we identify distinct roles for Celsr3 and Celsr2, as Celsr3 is required for startle circuit development while Celsr2 is dispensable, though Celsr2 can partially compensate for loss of Celsr3 in Mauthner cells. This contrasts with facial branchiomotor neuron migration in the hindbrain, which requires Celsr2 while we find that Celsr3 is dispensable. Combined, our data uncover critical and distinct roles for individual PCP components during assembly of the acoustic startle hindbrain circuit.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acoustic startle response / Acoustics / Animals / Axon guidance / Axon Guidance - physiology / Axons - metabolism / Axons - physiology / Behavior / Bias / Biology and Life Sciences / Brain / Cadherins / Cadherins - genetics / Cadherins - metabolism / Cell Polarity - genetics / Celsr3 protein / Frizzled protein / Frizzled Receptors - genetics / Frizzled Receptors - metabolism / Functional morphology / Genetic aspects / Hindbrain / Mauthner cells / Medicine and Health Sciences / Muscle contraction / Neural networks / Neurons / Neurons - metabolism / Neurons - physiology / Physical Sciences / Physiological aspects / Proteins / Reflex, Startle - physiology / Rhombencephalon / Rhombencephalon - metabolism / Roles / Siblings / Startle response / Synapses / Synapses - genetics / Synapses - metabolism / Synapses - physiology / Synaptogenesis / Zebrafish / Zebrafish - genetics / Zebrafish Proteins - genetics / Zebrafish Proteins - metabolism