Sequential addition of neuronal stem cell temporal cohorts generates a feed-forward circuit in the larval nerve cord.

How circuits self-assemble starting from neuronal stem cells is a fundamental question in developmental neurobiology. Here, we addressed how neurons from different stem cell lineages wire with each other to form a specific circuit motif. In larvae, we combined developmental genetics (twin-spot mosaic analysis with a repressible cell marker, multi-color flip out, permanent labeling) with circuit analysis (calcium imaging, connectomics, network science).

Development of motor circuits: From neuronal stem cells and neuronal diversity to motor circuit assembly.

In this review, we discuss motor circuit assembly starting from neuronal stem cells. Until recently, studies of neuronal stem cells focused on how a relatively small pool of stem cells could give rise to a large diversity of different neuronal identities. Historically, neuronal identity has been assayed in embryos by gene expression, gross anatomical features, neurotransmitter expression, and physiological properties.

Temporal transcription factors determine circuit membership by permanently altering motor neuron-to-muscle synaptic partnerships.

How circuit wiring is specified is a key question in developmental neurobiology. Previously, using the motor system as a model, we found the classic temporal transcription factor Hunchback acts in NB7-1 neuronal stem cells to control the number of NB7-1 neuronal progeny form functional synapses on dorsal muscles (Meng et al., 2019).

How prolonged expression of Hunchback, a temporal transcription factor, re-wires locomotor circuits.

How circuits assemble starting from stem cells is a fundamental question in developmental neurobiology. We test the hypothesis that, in neuronal stem cells, temporal transcription factors predictably control neuronal terminal features and circuit assembly. Using the Drosophila motor system, we manipulate expression of the classic temporal transcription factor Hunchback (Hb) specifically in the NB7-1 stem cell, which produces U motor neurons (MNs), and then we monitor dendrite morphology and neuromuscular synaptic partnerships.

Temporal Cohorts of Lineage-Related Neurons Perform Analogous Functions in Distinct Sensorimotor Circuits.

Neuronal stem cell lineages are the fundamental developmental units of the brain, and neuronal circuits are the fundamental functional units of the brain. Determining lineage-circuitry relationships is essential for deciphering the developmental logic of circuit assembly. While the spatial distribution of lineage-related neurons has been investigated in a few brain regions [1-9], an important, but unaddressed question is whether temporal information that diversifies neuronal progeny within a single lineage also impacts circuit assembly.