visualize-drosophila-leg-motor-neuron-axons-through-the-adult-cuticle

Visualize <em>Drosophila</em> Leg Motor Neuron Axons Through the Adult Cuticle

The majority of work on the neuronal specification has been carried out in genetically and physiologically tractable models such as C. elegans, Drosophila ...

NYU School of Medicine

Control of movement relies on the ability of circuits within the spinal cord to establish connections with specific subtypes of motor neuron (MN). Although the pattern of output from locomotor networks can be influenced by MN position and identity, whether MNs exert an instructive role in shaping synaptic specificity within the spinal cord is unclear. We show that Hox transcription-factor-dependent programs in MNs are essential in establishing the central pattern of connectivity within the ventral spinal cord. Transformation of axially projecting MNs to a limb-level lateral motor column (LMC) fate, through mutation of the Hoxc9 gene, causes the central afferents of limb proprioceptive sensory neurons to target MNs connected to functionally inappropriate muscles. MN columnar identity also determines the pattern and distribution of inputs from multiple classes of premotor interneurons, indicating that MNs broadly influence circuit connectivity. These findings indicate that MN-intrinsic programs contribute to the initial architecture of locomotor circuits.

Columnar-Intrinsic Cues Shape Premotor Input Specificity in Locomotor Circuits.

Motor output varies along the rostro-caudal axis of the tetrapod spinal cord. At limb levels, ∼60 motor pools control the alternation of flexor and extensor muscles about each joint, whereas at thoracic levels as few as 10 motor pools supply muscle groups that support posture, inspiration, and expiration. Whether such differences in motor neuron identity and muscle number are associated with segmental distinctions in interneuron diversity has not been resolved. We show that select combinations of nineteen transcription factors that specify lumbar V1 inhibitory interneurons generate subpopulations enriched at limb and thoracic levels. Specification of limb and thoracic V1 interneurons involves the Hox gene Hoxc9 independently of motor neurons. Thus, early Hox patterning of the spinal cord determines the identity of V1 interneurons and motor neurons. These studies reveal a developmental program of V1 interneuron diversity, providing insight into the organization of inhibitory interneurons associated with differential motor output.

Origin and Segmental Diversity of Spinal Inhibitory Interneurons.

Walking is the predominant locomotor behavior expressed by land-dwelling vertebrates, but it is unknown when the neural circuits that are essential for limb control first appeared. Certain fish species display walking-like behaviors, raising the possibility that the underlying circuitry originated in primitive marine vertebrates. We show that the neural substrates of bipedalism are present in the little skate Leucoraja erinacea, whose common ancestor with tetrapods existed ∼420 million years ago. Leucoraja exhibits core features of tetrapod locomotor gaits, including left-right alternation and reciprocal extension-flexion of the pelvic fins. Leucoraja also deploys a remarkably conserved Hox transcription factor-dependent program that is essential for selective innervation of fin/limb muscle. This network encodes peripheral connectivity modules that are distinct from those used in axial muscle-based swimming and has apparently been diminished in most modern fish. These findings indicate that the circuits that are essential for walking evolved through adaptation of a genetic regulatory network shared by all vertebrates with paired appendages. VIDEO ABSTRACT.

Article	Year
Columnar-Intrinsic Cues Shape Premotor Input Specificity in Locomotor Circuits. Cell reports\| PubMed ID: 29069594	2017
Origin and Segmental Diversity of Spinal Inhibitory Interneurons. Neuron\| PubMed ID: 29307712	2018
The Ancient Origins of Neural Substrates for Land Walking. Cell\| PubMed ID: 29425489	2018

Myungin Baek

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