Human disorders of axon guidance

Nugent, Alicia A.; Kolpak, Adrianne L.; Engle, Elizabeth C.

doi:10.1016/j.conb.2012.02.006

Cited by 76 publications

(63 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, we do not understand how these individual regulators functionally integrate into the common cytoskeletal machinery that ultimately implements neuronal behaviours. This deficit also leaves us with little means to explain the cellular aberrations caused by mutations of genes encoding ABPs or MTBPs that have been linked to brain disorders, including disorders of neurodevelopment and axonal growth (supplementary material Table S1) (Nugent et al, 2012;Tischfield et al, 2011).…”

Section: Box 1 Abps and Mtbps As Essential Regulators Of Cytoskeletamentioning

confidence: 99%

Using fly genetics to dissect the cytoskeletal machinery of neurons during axonal growth and maintenance

Prokop

Beaven

et al. 2013

Journal of Cell Science

View full text Add to dashboard Cite

SummaryThe extension of long slender axons is a key process of neuronal circuit formation, both during brain development and regeneration. For this, growth cones at the tips of axons are guided towards their correct target cells by signals. Growth cone behaviour downstream of these signals is implemented by their actin and microtubule cytoskeleton. In the first part of this Commentary, we discuss the fundamental roles of the cytoskeleton during axon growth. We present the various classes of actin-and microtubule-binding proteins that regulate the cytoskeleton, and highlight the important gaps in our understanding of how these proteins functionally integrate into the complex machinery that implements growth cone behaviour. Deciphering such machinery requires multidisciplinary approaches, including genetics and the use of simple model organisms. In the second part of this Commentary, we discuss how the application of combinatorial genetics in the versatile genetic model organism Drosophila melanogaster has started to contribute to the understanding of actin and microtubule regulation during axon growth. Using the example of dystonin-linked neuron degeneration, we explain how knowledge acquired by studying axonal growth in flies can also deliver new understanding in other aspects of neuron biology, such as axon maintenance in higher animals and humans.

show abstract

Section: Box 1 Abps and Mtbps As Essential Regulators Of Cytoskeletamentioning

confidence: 99%

Using fly genetics to dissect the cytoskeletal machinery of neurons during axonal growth and maintenance

Prokop

Beaven

et al. 2013

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Axon guidance is critical in brain development, and deregulation of this process may be implicated in certain mental diseases (Nugent et al 2012). The growth cone is a specialized neuron compartment that integrates guidance signals (Vitriol and Zheng 2012).…”

Section: From Attraction To Retraction: Dock1 Regulates Rac In Neuronmentioning

confidence: 99%

Insights into the biological functions of Dock family guanine nucleotide exchange factors

2014

View full text Add to dashboard Cite

Rho GTPases play key regulatory roles in many aspects of embryonic development, regulating processes such as differentiation, proliferation, morphogenesis, and migration. Two families of guanine nucleotide exchange factors (GEFs) found in metazoans, Dbl and Dock, are responsible for the spatiotemporal activation of Rac and Cdc42 proteins and their downstream signaling pathways. This review focuses on the emerging roles of the mammalian DOCK family in development and disease. We also discuss, when possible, how recent discoveries concerning the biological functions of these GEFs might be exploited for the development of novel therapeutic strategies.

show abstract

“…The precise alignment and coordinated movement of the eyes create a sensitive system to identify pathologic innervation of the extraocular muscles (EOMs) that arises during development (1,2). Neurogenic forms of strabismus serve as models to investigate axon guidance mechanisms that are relevant to human development.…”

Section: Introductionmentioning

confidence: 99%

Mutant α2-chimaerin signals via bidirectional ephrin pathways in Duane retraction syndrome

Nugent¹,

Park²,

Wei³

et al. 2017

Journal of Clinical Investigation

View full text Add to dashboard Cite

Duane retraction syndrome (DRS) is the most common form of congenital paralytic strabismus in humans and can result from α2-chimaerin (CHN1) missense mutations. We report a knockin α2-chimaerin mouse (Chn1 abducens neurons use bidirectional ephrin signaling via mutant α2-chimaerin to direct growth, while cervical spinal neurons use only ephrin forward signaling, and trochlear neurons do not use ephrin signaling. These findings reveal a role for ephrin bidirectional signaling upstream of mutant α2-chimaerin in DRS, which may contribute to the selective vulnerability of abducens motor neurons in this disorder.

show abstract

Human disorders of axon guidance

Cited by 76 publications

References 53 publications

Using fly genetics to dissect the cytoskeletal machinery of neurons during axonal growth and maintenance

Using fly genetics to dissect the cytoskeletal machinery of neurons during axonal growth and maintenance

Insights into the biological functions of Dock family guanine nucleotide exchange factors

Mutant α2-chimaerin signals via bidirectional ephrin pathways in Duane retraction syndrome

Contact Info

Product

Resources

About