Functional analysis of BMP4 signaling in mouse neural development

During early mouse neural development, bone morphogenetic protein (BMP) signaling patterns the dorsal neural tube and defines distinct neural progenitor cell domains along the dorsoventral axis. Unlike the ventral signaling molecule Sonic hedgehog, which has long-range activity by establishing a concentration gradient in the ventral neural tube, these dorsally expressed BMPs appear to have a limited domain of action. This raises questions as to how BMP activity is restricted locally and how restricted BMP signaling directs dorsal neural patterning and differentiation. I hypothesize that BMPs are restricted in the dorsal neural tube for correct dorsoventral patterning. ^ Previous studies have shown that the positively charged basic amino acids located at the N-terminus of several BMPs are essential for heparin binding and diffusion. This provides a novel tool to address these questions. Here I adapted a UAS/GAL4 bigenic mouse system to control the ectopic expression of BMP4 and a mutant form of BMP4 that lacks a subset of the N-terminal basic amino acids. The target genes, UAS-Bmp4 and UAS-mBmp4 , were introduced into the Hprt locus by gene targeting in mouse embryonic stem cells. The expression of the GAL4 transactivator was driven by a roof plate specific Wnt1 promoter. ^ The bigenic mouse embryos exhibit phenotype variations, ranging from mid/hindbrain defects, hemorrhage, and eye abnormalities to vasculture formation. Embryonic death starts around E11.5 because of severe hemorrhage. The different expression levels of the activated transgene may account for the phenotype variation. Further marker analysis reveals that mutant BMP4 induces ectopic expression of the dorsal markers MSX1/2 and PAX7 in the ventral neural tube. In addition, the expression of the ventral neural marker NKX2.2 is affected by the expanded BMP4 activity, indicating that ectopic BMP signaling can antagonize ventral signaling. Comparison of the phenotypes of the Wnt1/ Bmp4 and Wnt1/mBmp4 bigenic embryos that express transgenes at the same level, respectively, shows that mutant BMP4 causes the expansion of dorsal neural fates ventrally while wild type BMP4 does not, suggesting that mutant BMP4 acts farther than wild type BMP4. Together, these data suggest that the N-terminus basic amino acid core controls BMP4 long-range activity in neural development, and that BMP signaling patterns the dorsal neural tube through a secondary signaling pathway that involves homeodomain transcription factors MSX1/2 and PAX7. ^

Cary's Illustrated and Priced Catalogue: Surgical Instruments, Physicians, Hospital Supplies, and Furnishings, Druggist Sundries, Etc.

Second Edition. Pp.5-61 General Surgical Necessities, Gauze, Antiseptic Sundries, Surgical Sundries, Rubber Bandages, Catheters, Bougies, Splints, Tents, Emergency Bags, Surgeon's Needles, Operating Instruments, Amputating, Forceps, Aspiration, Cases, Catheters and Directors, Pocket Case Instruments, Dissecting and Post-Mortem Pp.62-118 General Operating - Osteotomy, Mastoid, Trephining, Eye Instruments, Aural, Nasal, Mouth and Throat, Tooth Forceps, Laryngoscopic Sets, Hydraulic Air Compressor, Variocele, Genito Urinary Pp. 119-167 Genito Urinary-Lithotrity, Alimentary, Anal and Rectal, Gynaecological, Pessaries, Microscopes, Syringes Pp.168-205 Chemical Apparatus and Glassware, Physician's Cabinets, Office Furniture, Operating Chairs and Tables, Hospital Beds, Cautery, Electrolytic, Batteries Pp.206-246 Cases, Varicose, Braces, Abdominal Supporters, Trusses, Invalid Chairs and Supplies, Sterilizers, Saddle-Bags, Deformity Apparatus Advertisements: Bandages, Abdominal Supporters, Rubber Supplies, Bags, Batteries, Cotton, Microscopes, Hypodermic Tablets, Atomizers, Furniture, Sterilizers, Syringes

Illustrated Catalogue of Standard Surgical Instruments and Allied Lines

Section "A": Dissecting and Post-Mortem Instruments Diagnostic Instruments and Apparatus Microscopes and Microscopic Accessories Laboratory Apparatus and Glass Ware Apparatus for Blood and Urine Analysis Apparatus for Phlebotomy, Cupping and Leeching Apparatus for Infusion and Transfusion Syringes for Aspiration and Injection Osteological Preparations Section "B": Anaesthetic, General Operating, Osteotomy, Trepanning, Bullet, Pocket Case, Cautery, Ligatures, Sutures, Dressings, Etc. Section "B" continued Section "C": Eye, Ear, Nasal, Dermal, Oral, Tonsil, Tracheal, Laryngeal,Esophageal, Stomach, Intestinal, Gall Bladder Section "C": continued Section "D": Rectal, Phimosis, Prostatic, Vesical, Urethral, Ureteral, Instruments Section "E": Gynecic, Hysterectomy, Obstetrical, Instrument Satchels, Medicine Cases Section "F": Electric Cautery Transformers, Electro-Cautery Burners and Accessories, Electric Current Controllers, Electro-Diagnostic Outfits, Electrolysis Instruments Electro-Therapeutic Lamps, Faradic Batteries, Galvanic Batteries Section "G": Office Furniture, Office Sterilizing Apparatus, Hospital Supplies, Surgical Rubber Goods, Sick Room Utensils, Invalid Rolling Chairs, Invalid Supplies Section "H": Artificial Limbs, Deformity Apparatus, Fracture Apparatus, Splints, Splint Material, Elastic Hosiery, Abdominal Supporters, Crutches, Trusses, Suspensories, Etc. Index

Understanding and Fostering Family Resilience

This paper examines a model of resilience and provides a fictional case example from the classical musical, Fiddler on the Roof along with a discussion of how this model may be helpful in assisting families at various levels of functioning to bounce back and perhaps even experience growth through facing difficult challenges.