+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Fragile X mental retardation protein is required for programmed cell death and clearance of developmentally-transient peptidergic neurons

, : Fragile X mental retardation protein is required for programmed cell death and clearance of developmentally-transient peptidergic neurons. Developmental Biology 356(2): 291-307

Fragile X syndrome (FXS), caused by loss of fragile X mental retardation 1 (FMR1) gene function, is the most common heritable cause of intellectual disability and autism spectrum disorders. The FMR1 product (FMRP) is an RNA-binding protein best established to function in activity-dependent modulation of synaptic connections. In the Drosophila FXS disease model, loss of functionally-conserved dFMRP causes synaptic overgrowth and overelaboration in pigment dispersing factor (PDF) peptidergic neurons in the adult brain. Here, we identify a very different component of PDF neuron misregulation in dfmr1 mutants: the aberrant retention of normally developmentally-transient PDF tritocerebral (PDF-TRI) neurons. In wild-type animals, PDF-TRI neurons in the central brain undergo programmed cell death and complete, processive clearance within days of eclosion. In the absence of dFMRP, a defective apoptotic program leads to constitutive maintenance of these peptidergic neurons. We tested whether this apoptotic defect is circuit-specific by examining crustacean cardioactive peptide (CCAP) and bursicon circuits, which are similarly developmentally-transient and normally eliminated immediately post-eclosion. In dfmr1 null mutants, CCAP/bursicon neurons also exhibit significantly delayed clearance dynamics, but are subsequently eliminated from the nervous system, in contrast to the fully persistent PDF-TRI neurons. Thus, the requirement of dFMRP for the retention of transitory peptidergic neurons shows evident circuit specificity. The novel defect of impaired apoptosis and aberrant neuron persistence in the Drosophila FXS model suggests an entirely new level of "pruning" dysfunction may contribute to the FXS disease state.


PMID: 21596027

DOI: 10.1016/j.ydbio.2011.05.001

Other references

Vargas Rubiano, Alfonso, 1956: Application of chlortetracycline as growth factor in 92 infants. In 92 lactants of less than 6 months, growth was increased during the days on which they received 20 mgs of aureomycin besides their normal diet.

Weichert W.; Grun H.; Muether B.; Steinhoff W.; Breddin H.K., 1985: Effects of prostaglandins on platelet function and laser induced thrombus formation in rat mesenteric arterioles. Schroer, K (Ed ) Prostaglandins And Other Eicosanoids in The Cardiovascular System: Experimental Data: Clinical Experience; 2nd International Symposium on Prostaglandins, Nuernberg-Fuerth, West Germany, May 9-11, 1984 Xiv+572p S Karger Ag: Basel, Switzerland; New York, N Y , Usa Illus 303-309

Alexander, Edward J., 1939: Strophanthus preussii. Addisonia 21(1): 15-16

Saifer, P.; Saifer, M., 1987: Clinical detection of sensitivity to preservatives and chemicals. Food allergy and intolerance edited by Jonathan Brostoff Stephen J Challacombe: 424

Kitamura, T., 1993: Lentiviruses and origin of HIV. Nihon Rinsho. Japanese Journal of Clinical Medicine 51 Suppl: 103-110

Pal, B.; Li, Z.; Takenaka, S.; Tsuyama, S.; Kitagawa, T., 2003: Synergistic activation of soluble guanylate cyclase by CO and YC-1 Effects of substrate. Journal of Inorganic Biochemistry 96(1): 209, 15 July

Witzeman J.S., 1990: The transacetoacetylation reaction mechanistic implications. Tetrahedron Letters 31(10): 1401-1404

Galvin, N.J.; Vance, P.M.; Dixit, V.M.; Fink, B.; Frazier, W.A., 1987: Interaction of human thrombospondin with types I-V collagen: direct binding and electron microscopy. Binding of thrombospondin (TSP) to types I-V collagen was examined by direct binding assays using 125I-TSP and by visualization of rotary-shadowed intermolecular complexes in the electron microscope. The binding of TSP was highest to type V collag...

Zhu, P-Yuan.; Yan, J-Mei.; Xue, M.; Ye, D.; Yao, G-Hong.; Luan, J-Feng., 2014: A case of dispermic chimerism with normal phenotype identified during ABO blood grouping. Human chimerism with normal phenotype derived from the fusion of two different zygotes is a rare phenomenon. We describe a case of a phenotypically normal 17-year-old diagnosed with dispermic chimerism during routine ABO blood grouping. ABO groupi...

Ogilvie; Adloff; Begemann-Blaich; Bouissou; Hubele; Imme; Iori; Kreutz; Kunde; Leray; Lindenstruth; Liu; Lynen; Meijer; Milkau; Müller; Ng; Pochodzalla; Raciti; Rudolf; Sann; Schüttauf; Seidel; Stuttge; Trautmann; Tucholski, 1991: Rise and fall of multifragment emission. Physical Review Letters 67(10): 1214-1217