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An Explant Assay for Assessing Cellular Behavior of the Cranial Mesenchyme
Published on: January 20, 2013
Retinal axon misrouting at the optic chiasm in mice with neural tube closure defects
R A Rachel1, J N Murdoch, F Beermann
1Center for Neurobiology and Behavior, Columbia University, New York, New York, USA. rar30@columbia.edu
Abstract:
In a new mouse mutant, circletail (Crc), failure of neural tube closure (embryonic day [E] 8-9) is associated with errors in retinal axon projection at the optic chiasm (E12-18), such that many axons normally projecting contralaterally instead grow to ipsilateral targets. Although the architecture of the chiasmatic region is altered, neurons and glia containing putative cues for axon guidance are present. The aberrant ipsilateral-projecting cells originate from a nonrandom expansion of the wild-type uncrossed retinal region. These axon pathway defects are found in two other mutants with cephalic neural tube defects (NTD), loop-tail (Lp) and Pax3 (splotch; Sp(2H)). Crc is phenotypically similar to Lp, exhibiting an open neural tube from midbrain to tail (craniorachischisis), while splotch has spina bifida with or without a cranial NTD. The retinal axon abnormalities occur only in the presence of NTD and not in homozygous mutants lacking cranial NTD. Thus, failure of neural tube closure is associated with failure of many retinal axons to cross the ventral midline. This study therefore reveals an unexpected connection between closure of the neural tube at the dorsal midline and development of ventral axon tracts. genesis 27:32-47, 2000.
Insights
Neural tube defects in mice disrupt retinal axon guidance, causing misrouted axons at the optic chiasm. This study links dorsal neural tube closure to ventral axon tract development.
Area of Science:
- Developmental biology
- Neuroscience
- Genetics
Background:
- Neural tube closure is critical for proper brain development.
- Retinal axon guidance at the optic chiasm is essential for vision.
- Mouse mutants with neural tube defects (NTDs) offer insights into developmental processes.
Purpose of the Study:
- To investigate the relationship between neural tube closure defects and retinal axon guidance errors.
- To identify the specific impact of NTDs on optic chiasm development.
- To explore the connection between dorsal midline closure and ventral axon tract formation.
Main Methods:
- Analysis of the circletail (Crc) mouse mutant exhibiting NTDs.
- Examination of retinal axon projections at the optic chiasm during embryonic development (E12-18).
- Comparison with other NTD mutants (loop-tail and splotch) to identify commonalities.
Main Results:
- The Crc mutant shows failure of neural tube closure and aberrant retinal axon projections, with many axons misrouting to ipsilateral targets.
- These axon pathway defects are specifically associated with the presence of cephalic NTDs.
- Aberrant projections originate from an expanded uncrossed retinal region.
Conclusions:
- Failure of neural tube closure is directly linked to errors in retinal axon guidance at the optic chiasm.
- This study reveals an unexpected connection between dorsal neural tube closure and the development of ventral axon tracts.
- Proper development of ventral axon tracts depends on the integrity of neural tube closure.
