Mis-expression of L1 on pre-crossing spinal commissural axons disrupts pathfinding at the ventral midline

Imondi, Ralph; Jevince, Angela R.; Helms, Amy W.; Johnson, Jane E.; Kaprielian, Zaven

doi:10.1016/j.mcn.2007.08.003

Cited by 16 publications

(26 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whereas the Atoh1-tauGFP reporter has previously been shown to specifically label dI1 neurons [11,15], here, we demonstrate that a novel transgenic mouse line, Neurog2-tauGFP , targets GFP to a subset of the Neurog2 expressing progenitors in the dorsal neural tube that give rise to dI4 commissural neurons. We find that dI1, but not dI4, commissural axons express Npn2, and require this receptor for navigating on the contralateral side of the ventral midline and for Sema3-mediated collapse of their growth cones in vitro .…”

Section: Introductionmentioning

confidence: 54%

Neuropilin2 regulates the guidance of post-crossing spinal commissural axons in a subtype-specific manner

et al. 2013

Self Cite

View full text Add to dashboard Cite

BackgroundSpinal commissural axons represent a model system for deciphering the molecular logic that regulates the guidance of midline-crossing axons in the developing central nervous system (CNS). Whether the same or specific sets of guidance signals control the navigation of molecularly distinct subtypes of these axons remains an open and largely unexplored question. Although it is well established that post-crossing commissural axons alter their responsiveness to midline-associated guidance cues, our understanding of the repulsive mechanisms that drive the post-crossing segments of these axons away from the midline and whether the underlying guidance systems operate in a commissural axon subtype-specific manner, remains fragmentary at best.ResultsHere, we utilize axonally targeted transgenic reporter mice to visualize genetically distinct dorsal interneuron (dI)1 and dI4 commissural axons and show that the repulsive class 3 semaphorin (Sema3) guidance receptor Neuropilin 2 (Npn2), is selectively expressed on the dI1 population and is required for the guidance of post-crossing dI1, but not dI4, axons. Consistent with these observations, the midline-associated Npn2 ligands, Sema3F and Sema3B, promote the collapse of dI1, but not dI4, axon-associated growth cones in vitro. We also identify, for the first time, a discrete GABAergic population of ventral commissural neurons/axons in the embryonic mouse spinal cord that expresses Npn2, and show that Npn2 is required for the proper guidance of their post-crossing axons.ConclusionsTogether, our findings indicate that Npn2 is selectively expressed in distinct populations of commissural neurons in both the dorsal and ventral spinal cord, and suggest that Sema3-Npn2 signaling regulates the guidance of post-crossing commissural axons in a population-specific manner.

show abstract

Section: Introductionmentioning

confidence: 54%

Neuropilin2 regulates the guidance of post-crossing spinal commissural axons in a subtype-specific manner

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…Mice were genotyped by PCR as previously described: BmprIa flox (Mishina et al, 2002), BmprIb (Yi et al, 2000), Math1::tauGfp (Imondi et al, 2007), Math1::Cre (Matei et al, 2005), Rosa26R::Yfp (Srinivas et al, 2001 Whole-mount fillet preparations were dissected from the upper brachial to lower thoracic region of E10.5 spinal cords from the surrounding mesoderm in dispase-free medium. Spinal cords were cut along the FP at the ventral midline, embedded in collagen (BD Biosciences), fixed and immunostained.…”

Section: Generation and Analysis Of Mutant Micementioning

confidence: 99%

“…To address this question, we examined mice mutant for either BmprIa or BmprIb in combination with a genetically encoded Math1::tauGfp reporter, which expresses GFP in the dI1 population of dorsal commissural axons (Imondi et al, 2007;Hazen et al, 2012). Although BmprIb loss-of-function mutants are viable (Yi et al, 2000;Yi et al, 2001), the loss of BmprIa is lethal (Mishina et al, 1995).…”

Section: Commissural Neurons Deficient In Bmprib But Not Bmpria Extmentioning

confidence: 99%

“…As a first approach to examining whether the loss of BmprIa or BmprIb alters commissural axon outgrowth, we assessed the length of GFP + axons extending from dissociated control (Math1::Cre; (Geisert and Frankfurter, 1989) and a genetically encoded reporter, Math1::tauGfp (Imondi et al, 2007) Fig. 2A).…”

Section: Commissural Neurons Deficient In Bmprib But Not Bmpria Extmentioning

confidence: 99%

See 1 more Smart Citation

Type Ib BMP receptors mediate the rate of commissural axon extension through inhibition of cofilin activity

Yamauchi

Varadarajan

et al. 2013

Development

View full text Add to dashboard Cite

SUMMARYBone morphogenetic proteins (BMPs) have unexpectedly diverse activities establishing different aspects of dorsal neural circuitry in the developing spinal cord. Our recent studies have shown that, in addition to spatially orienting dorsal commissural (dI1) axons, BMPs supply 'temporal' information to commissural axons to specify their rate of growth. This information ensures that commissural axons reach subsequent signals at particular times during development. However, it remains unresolved how commissural neurons specifically decode this activity of BMPs to result in their extending axons at a specific speed through the dorsal spinal cord. We have addressed this question by examining whether either of the type I BMP receptors (Bmpr), BmprIa and BmprIb, have a role controlling the rate of commissural axon growth. BmprIa and BmprIb exhibit a common function specifying the identity of dorsal cell fate in the spinal cord, whereas BmprIb alone mediates the ability of BMPs to orient axons. Here, we show that BmprIb, and not BmprIa, is additionally required to control the rate of commissural axon extension. We have also determined the intracellular effector by which BmprIb regulates commissural axon growth. We show that BmprIb has a novel role modulating the activity of the actin-severing protein cofilin. These studies reveal the mechanistic differences used by distinct components of the canonical Bmpr complex to mediate the diverse activities of the BMPs.

show abstract

“…These viruses can be genetically targeted to specific classes of spinal neurons, by using the enhancer regions of developmentally relevant genes, such as transcription factors described above with restricted expression in the spinal cord, to direct the expression of viral receptors to specific classes of neurons (Wickersham et al, 2007). The use of developmental restricted enhancers, where suitable examples are available, has also been invaluable for directing the expression of fluorescent proteins epitope tagged with either membrane or axonal localization signals, such as tau (Mombaerts et al, 1996), to specific axonal pathways in the mouse spinal cord (Bai et al, 2011; Imondi et al, 2007). Examples in the spinal cord include the Math1 enhancer, which drives the expression of markers specifically in dI1 commissural axons (Hazen et al, 2012; Helms and Johnson, 1998; Phan et al, 2010) and the Hb9 enhancer, which can drive the expression of heterologous genes in spinal MNs (Arber et al, 1999) and is invaluable for dissecting the branching patterns of motor nerves in the limb (De Marco Garcia and Jessell, 2008; Rousso et al, 2008).…”

Section: Cell Lineage Studies In the Developing Peripheral And Centramentioning

confidence: 99%

From classical to current: Analyzing peripheral nervous system and spinal cord lineage and fate

Butler

Bronner‐Fraser

2015

Developmental Biology

View full text Add to dashboard Cite

During vertebrate development, the central (CNS) and peripheral nervous systems (PNS) arise from the neural plate. Cells at the margin of the neural plate give rise to neural crest cells, which migrate extensively throughout the embryo, contributing to the majority of neurons and all of the glia of the PNS. The rest of the neural plate invaginates to form the neural tube, which expands to form the brain and spinal cord. The emergence of molecular cloning techniques and identification of fluorophores like Green Fluorescent Protein (GFP), together with transgenic and electroporation technologies, have made it possible to easily visualize the cellular and molecular events in play during nervous system formation. These lineage-tracing techniques have precisely demonstrated the migratory pathways followed by neural crest cells and increased knowledge about their differentiation into PNS derivatives. Similarly, in the spinal cord, lineage-tracing techniques have led to a greater understanding of the regional organization of multiple classes of neural progenitor and post-mitotic neurons along the different axes of the spinal cord and how these distinct classes of neurons assemble into the specific neural circuits required to realize their various functions. Here, we review how both classical and modern lineage and marker analyses have expanded our knowledge of early peripheral nervous system and spinal cord development.

show abstract

Mis-expression of L1 on pre-crossing spinal commissural axons disrupts pathfinding at the ventral midline

Cited by 16 publications

References 43 publications

Neuropilin2 regulates the guidance of post-crossing spinal commissural axons in a subtype-specific manner

Neuropilin2 regulates the guidance of post-crossing spinal commissural axons in a subtype-specific manner

Type Ib BMP receptors mediate the rate of commissural axon extension through inhibition of cofilin activity

From classical to current: Analyzing peripheral nervous system and spinal cord lineage and fate

Contact Info

Product

Resources

About