Expression of PLA2G6 in human fetal development: Implications for infantile neuroaxonal dystrophy
Brenda Polster1, Moira Crosier, Susan Lindsay
1Molecular and Medical Genetics, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, United States. polsterb@ohsu.edu
Insights
Mutations in PLA2G6 cause infantile neuroaxonal dystrophy (INAD). This study reveals PLA2G6 is crucial for early brain development, particularly in neural stem cells and maturing neurons, suggesting INAD may begin before birth.
Area of Science:
- Developmental biology
- Neuroscience
- Genetics
Background:
- Infantile neuroaxonal dystrophy (INAD) is an autosomal recessive disorder caused by mutations in PLA2G6.
- PLA2G6 encodes calcium-independent phospholipase A(2) group VIA (iPLA2-VIA).
- INAD presents in infancy with optic atrophy and psychomotor regression.
Purpose of the Study:
- To investigate the expression pattern of PLA2G6 during early human embryonic development.
- To understand the role of PLA2G6 in neurodevelopment and its potential implications for INAD pathogenesis.
Main Methods:
- In situ hybridization was used to examine PLA2G6 expression in human embryonic tissues.
- Expression patterns were analyzed at various Carnegie Stages (CS) and post-conception weeks (PCW).
Main Results:
- PLA2G6 expression was detected in the ventricular zone of the midbrain and forebrain at CS19, indicating expression in neural stem and progenitor cells.
- By CS23, expression expanded to the hindbrain VZ and neocortical SVZ, ganglionic eminences, and diencephalon.
- Strong expression was observed in post-mitotic cortical plate neurons by 9PCW, as well as in the developing eye (lens and retina), spinal cord, dorsal root ganglia, and non-neuronal tissues.
Conclusions:
- PLA2G6 plays a significant role in neuronal proliferation throughout brain development and in maturing neurons.
- The dynamic expression pattern suggests that INAD pathogenesis may initiate during prenatal development.
- Understanding PLA2G6's developmental role is crucial for insights into INAD etiology.
Abstract:
Mutations in PLA2G6, which encodes calcium-independent phospholipase A(2) group VIA (iPLA2-VIA), underlie the autosomal recessive disorder infantile neuroaxonal dystrophy (INAD). INAD typically presents in the first year of life, and leads to optic atrophy and psychomotor regression. We have examined PLA2G6 expression in early human embryonic development by in situ hybridization. At Carnegie Stage (CS) 19 (approximately 7 post-conception weeks [PCW]), strong expression is evident in the ventricular zone (VZ) of midbrain and forebrain suggestive of expression in neural stem and progenitor cells. At CS23 (8PCW) expression is also detectable in the VZ of the hindbrain and the subventricular zone (SVZ) of the developing neocortex, ganglionic eminences and diencephalon. By 9PCW strong expression in the post-mitotic cells of the cortical plate can be seen in the developing neocortex. In the eye, expression is seen in the lens and retina at all stages examined. PLA2G6 expression is also evident in the alar plate of the spinal cord, dorsal root ganglia, the retina and lens in the eye and several non-neuronal tissues, including developing bones, lung, kidney and gut. These findings suggest a role for PLA2G6 in neuronal proliferation throughout the developing brain and in maturing neurons in the cortical plate and hindbrain. Although widespread PLA2G6 expression is detected in neuronal tissues, the pattern shows dynamic changes with time and indicates that INAD pathogenesis may begin prior to birth.
